Included as part of the "PRECAUTIONS" Section
For Intravenous Use Only
Fatal If Given By Other Routes
Fatal if given by other routes. Death has occurred with intrathecal use.
Marqibo (vinCRIStine sulfate LIPOSOME injection) has different dosage recommendations than vinCRIStine sulfate injection. Verify drug name and dose prior to preparation and administration to avoid overdosage [see DOSAGE AND ADMINISTRATION].
Extravasation Tissue Injury
Extravasation can occur with Marqibo and extravasation causes tissue injury. Only administer through a secure and free-flowing venous access line. If extravasation is suspected, discontinue infusion immediately and consider local treatment measures.
Sensory and motor neuropathies are common and are cumulative. Monitor patients for symptoms of peripheral motor and sensory, central and autonomic neuropathy, such as hypoesthesia, hyperesthesia, paresthesia, hyporeflexia, areflexia, neuralgia, jaw pain, decreased vibratory sense, cranial neuropathy, ileus, burning sensation, arthralgia, myalgia, muscle spasm, or weakness, both before and during treatment. Orthostatic hypotension may occur. The risk of neurologic toxicity is greater if Marqibo is administered to patients with preexisting neuromuscular disorders or when other drugs with risk of neurologic toxicity are being given. In the studies of relapsed and/or refractory adult ALL patients, Grade ≥ 3 neuropathy events occurred in 32.5% of patients.
Patients with preexisting severe neuropathy should be treated with Marqibo only after careful risk-benefit assessment. Interrupt, reduce the dose, or discontinue Marqibo based on severity [see DOSAGE AND ADMINISTRATION].
Neutropenia, thrombocytopenia, or anemia may occur with Marqibo. Monitor complete blood counts prior to each dose of Marqibo. For Grade 3 or 4 neutropenia, thrombocytopenia, or anemia, consider Marqibo dose delay or reduction, as well as supportive care measures.
Tumor Lysis Syndrome
Tumor lysis syndrome (TLS) may occur in patients with ALL receiving Marqibo. Anticipate, monitor for, and manage as appropriate.
Constipation And Bowel Obstruction
Ileus, bowel obstruction, and colonic pseudo-obstruction have occurred. Marqibo can cause constipation [see ADVERSE REACTIONS].
Institute a prophylactic bowel regimen to mitigate potential constipation, bowel obstruction, and paralytic ileus. Consider adequate dietary fiber intake, hydration, and stool softeners. Use additional laxative products as needed.
Marqibo can cause severe fatigue. Consider dose delay, reduction, or discontinuation of Marqibo as appropriate.
Fatal hepatic toxicity and increased aspartate aminotransferase (AST) occurred. Grade ≥3 increased AST occurred in 6% to 11% of patients in clinical trials. Monitor hepatic function tests. Interrupt or reduce the dose of Marqibo as appropriate.
Based on findings from nonclinical studies and the mechanism of action, Marqibo can cause fetal harm when administered to a pregnant woman. In toxicology studies in rats, vincristine sulfate liposome injection was teratogenic and caused embryo-fetal mortality at exposures less than those reported in patients at the recommended dose.
Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with Marqibo and for 6 months after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with Marqibo and for 3 months after the last dose [see Use In Specific Populations].
Carcinogenesis, Mutagenesis, Impairment Of Fertility
No carcinogenicity studies have been conducted with Marqibo or non-liposomal vincristine sulfate. Based on the mechanism of action and genotoxicity findings in nonclinical studies conducted with non-liposomal vincristine sulfate, Marqibo may be carcinogenic.
No genotoxicity studies have been conducted with Marqibo. Non-liposomal vincristine was genotoxic in in vitro and in vivo studies.
The single-and repeat-dose animal toxicology study results indicate that Marqibo can impair male fertility, consistent with the literature on non-liposomal vincristine sulfate. Administration of vincristine liposome injection to rats at dose levels comparable to the recommended clinical dose caused testicular degeneration and atrophy, and epididymal aspermia. Adverse effects in male reproductive organs were not reversible following a 14 day recovery period.
Use In Specific Populations
Based on findings from nonclinical studies and its mechanism of action, Marqibo can cause fetal harm when administered to a pregnant woman [see CLINICAL PHARMACOLOGY, Nonclinical Toxicology]. There are insufficient data on use of vincristine sulfate in pregnant women to evaluate for a drug-associated risk. In animal reproduction studies, intravenous administration of vincristine sulfate liposome injection to pregnant rats during organogenesis caused adverse developmental outcomes including increased embryo-fetal mortality, alterations to growth, and structural abnormalities (see Data). Advise pregnant women of the potential risk to a fetus.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
In an embryo-fetal developmental study, pregnant rats were administered vincristine sulfate liposome injection intravenously during the period of organogenesis at vincristine sulfate doses of 0.022 to 0.09 mg/kg/day. Drug-related adverse effects included fetal malformations (skeletal and visceral), decreases in fetal weights, increased numbers of early resorptions and post-implantation losses, and decreased maternal body weights Malformations were observed at doses ≥ 0.044 mg/kg/day in animals at systemic exposures approximately 20-40% of those reported in patients at the recommended dose.
There are no data on the presence of vincristine sulfate or its metabolites in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with Marqibo and for at least 1 week after the last dose.
Females And Males Of Reproductive Potential
Marqibo can cause fetal harm when administered to a pregnant woman [see Pregnancy].
Verify the pregnancy status in females of reproductive potential prior to initiating Marqibo.
Advise females of reproductive potential to use effective contraception during treatment with Marqibo and for 6 months after the last dose.
Based on genotoxicity findings with non-liposomal vincristine, advise males with female partners of reproductive potential to use effective contraception during treatment with Marqibo and for 3 months after the last dose [see Nonclinical Toxicology].
Based on findings in humans with non-liposomal vincristine sulfate and in animals administered vincristine sulfate liposome injection, Marqibo may impair fertility.
Gonadal dysfunction has been reported in both male and female post-pubertal patients who received multi-agent chemotherapy, including non-liposomal vincristine sulfate. The degree to which testicular or ovarian functions are affected is age-, dose-, and agent-dependent. Recovery may occur in some, but not all patients.
In animals, adverse effects on male reproductive organs were not reversible after a recovery period [see Nonclinical Toxicology].
The safety and effectiveness of Marqibo in pediatric patients have not been established.
Of the total number of patients in clinical studies of Marqibo, 11% were aged 65 years or older. Clinical studies of Marqibo did not include sufficient numbers of patients aged 65 and older to determine whether they respond differently from younger patients. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Monitor patients closely for adverse reactions, including hepatic toxicity. No dose adjustment is recommended for patients with mild or moderate hepatic impairment. The influence of severe hepatic impairment on the exposure, safety and efficacy of Marqibo has not been evaluated.